Tuesday, December 18, 2012

What is Parabon's technology? I don't understand it.

..."We can now 'print,' molecule by molecule, exactly the compound that we want," says Steven Armentrout, the principal investigator on the NSF grants and co-developer of Parabon's technology. "What differentiates our nanotechnology from others is our ability to rapidly, and precisely, specify the placement of every atom in a compound that we design."

..."When designing a therapeutic compound, we combine knowledge of the cell receptors we are targeting or biological pathways we are trying to affect with an understanding of the linking chemistry that defines what is possible to assemble," says Hong Zhong, senior research scientist at Parabon and a collaborator on the grants. "It's a deliberate and methodical engineering process, which is quite different from most other drug development approaches in use today."

...The Parabon and Janssen researchers intend for their new prostate cancer drug to overcome several existing cancer-treatment obstacles. The drug design combines a toxin with a chemical that makes cancer cells susceptible to that toxin. Additionally, the drug incorporates components that improve delivery to cancer cells while avoiding healthy tissue, and chemical markers that allow researchers to monitor the drug's arrival at tumors. For the new compound, total design time plus synthesis time will be a matter of weeks.

..."Currently, most drugs are developed using a screening technique where you try a lot of candidate compounds against targets to 'see what sticks'," says Armentrout. "Instead, we're designing very specific drugs based on their molecular structure, with target molecules that bind to receptors on specific types of cancer cells. In plug-and-play fashion, we can swap in or swap out any of the functional components, as needed, for a range of treatment approaches."

Huh? I really don't quite understand what is going on here. What's worse is the Extreme Tech explanation for what is happening -- it makes even less sense. I'm going to highlight in bold the strangest sentences to this dumb chemist:

...While there are many applications in microelectronics, optics, and sensor technology where the ability to precisely engineer nanostructures would be invaluable, the ability to nanotailor drugs for treating cancer is ripe and low-hanging fruit...

Cancer medicines are typically so expensive that a real price per molecule can be discussed using familiar numbers.For this reason insurance companies do not want to be caught paying for any extra molecules if the prescription only requires a certain amount. They also want to be sure that the drug company is providing the amount claimed. Platinum for example, is more expensive than gold even before it is turned into a medicine. To use it as a cancer treatment, any sample must be pure and the quantity known, and regulated as such. Beyond that it must be turned into a molecule that the body can properly absorb, distribute to the right tissue, metabolize, and excrete in a way that ensures sufficient time to function. Each of these steps can add an order of magnitude to cost — and that’s just for simple metal ion.

...The DNA itself is not the drug. The DNA is the ferry that brings to bear the drug or other molecule of interest that is bound to it. The DNA also acts as the selector that tags the correct drug, the counter that determines its total number, and the matrix that stabilizes it in a permanent structure. Many cancers are currently treated with a medicinal cocktail, which for some reason is invariably prescribed as a combination of four drugs and designated with a four-letter word. The right blend for one patient is not the necessarily the proper one for the next, and neither is the dose. Excess drug and mismatch of inventory to demand is a problem no cancer treatment center wants to have, particularly when shelf life is limited. Hospital and pharmacy error is also a significant problem. On-demand DNA-based assembly suddenly makes many of these problems recede into the distance...

...The ability to program-in new functional molecules is nearly as limitless as one might have bar codes to track the vials in which store them. For drugs, your custom pill could also have all the other things that might be needed rolled into one. Drugs to treat the side-effects of the primary treatment, anti-nausea medicine, blood thinners, pain controllers, and whatever else.

For now, the methods that Parabon uses to create its starter molecules — the relatively short DNA strands to which a drug or other molecule is actually bound to — are synthesized by the trillions in identical form with standard methods, probably traditional PCR. This is not, in a strict sense, identified with the 3D printing methods of today. As the technology evolves, the “building of the house” may become more closely knit within the same platform to the “building of the city,” and PCR machines may evolve to become more like 3D printers. The extent to which this is already happening is tough to know, but we can be sure of one thing, it is definitely happening.

This is a big prank or something? Has this text been machine translated from the original Urdu?

If you look at the actual graphic that's involved, I think the idea is the following:

This DNA/drug hybrid could be used as a delivery vehicle -- and could be synthesized on demand at the hospital.

Parabon has invented a software program to help biologists design these drug hybrid macromolecules.

Anyone have a better idea of what it is?

Naturally, this is the problem when science gets translated by people who don't fully understand what's going on. Metaphors get mixed, language "sounds about right", and people press "publish"/"send" instead of sitting down and actually reading the text. (Besides, DNA-drug hybrid technology has been known for quite a while, right?)

15 comments:

The scary thing is that this was funded by the NSF!!!!! And you wonder what your and my tax dollars are doing - exactly, supporting awesome-sounding but not really awesome SciFi research.

And, a more serious comment - do these people know anything about the whole RNAi/gene delivery field at all? Aka the siRNA bubble? If one can effectively deliver highly charged oligos without toxicity/safety issues, they don't need tiny NSF grants.

"cancer medicines are typically so expensive that a real price per molecule can be discussed using familiar numbers."

To give the example they used, cis-platin costs ~100/gram. It has a MW of 300 g/mol. Based on my calculations that means that the price per molecule is about one attocent. Yup, those are familiar numbers to me, by golly!

The press release is quite confusing especially the sentence "The process, from conception to production, can be performed in weeks, or even days--much faster than traditional drug discovery techniques that rely on trial and error for screening potentially useful compounds." It seems that you are still relying on trial and error to choose which molecules will be in the pool that are attached to the DNA snippets. Can all potentially useful candidate molecules can easily be bound to DNA and oriented/ or released in vivo as you would want? Are these big frameworks supposed to sit on the surface of cancer cells or somehow pass their targets through the membranes? How can the in vivo screening can be done in only a few days- doesn't it take longer to determine how the cancer is responding to treatment or if the drug affects other bodily systems? These are questions that would help me, a non-synthetic, non-medicinal chemist understand the scope of Parabon's discovery better.

I actually work on projects in a related area. You are correct, this press release is a high-grade, unadulterated hype about research that is based pretty much on wishful thinking. Stuff like this gives a bad name to the entire field of nanoparticle/targeted drug delivery

(1) Steven Armentrout, Ph.D., President, has over 25 years experience designing and using high-performance computing solutions to solve large-scale problems in a wide range of domains ranging from financial forecasting, proteomics and satellite communications to genomic sequence analysis and climate modeling. In 1999, desiring a robust, scalable, on-demand computing platform, able to handle even the largest machine learning and data mining problems, which were then his focus, he founded Parabon Computation (PCI), today a leading cloud computing software company and majority shareholder of Parabon NanoLabs. Dr. Armentrout received a Ph.D. in Computer Science from the University of Maryland.

(2) Michael L. Norton, Ph.D., Co-Founder and Chief Science Officer, is also a Professor of Chemistry at Marshall University (MU). He first began working in the field of nanoscience in 1977, when he was a graduate student working with two-dimensional materials. He regularly participates in National Science Foundation, Department of Defense, and American Chemical Society Petroleum Research Fund proposal reviews. He earned a Ph.D. in Solid State Chemistry from Arizona State University and went on to pursue two years of post-graduate training in Optical and Electronic Materials at the Naval Weapons Center in China Lake, California.

(3) Christopher Dwyer, Ph.D., Co-Founder and Vice President, Research & Development, also serves as an associate professor of Electrical and Computer Engineering at Duke University. Dr. Dwyer has a unique combination of wet-lab and bit-lab experience. He received the 2009 Presidential Early Career Award for Scientists and Engineers (PECASE), the highest honor given to early career scientists by the US Government, is a Member of DARPA's 2009 Computer Science Study Group, and received a 2008 Young Investigator Award from the Army Research Office. Dr. Dwyer received a Ph.D. in Computer Science from the University of North Carolina at Chapel Hill.

Clearly, together these individuals command a wealth of knowledge as it relates to drug discovery, medicinal chemistry, and related fields!!!!!

It always has! It is part of the SBIR mandate.But that's not NSF alone. Add DoD, DARPA, etc. etc.

For awhile I made a living consulting start-ups as to how to get to the federal trough of money. Of which there are $$$$$.Until I couldn't take it any more. You think Parabon is the exception among small business grantees? More like the rule!

"Many cancers are currently treated with a medicinal cocktail, which for some reason is invariably prescribed as a combination of four drugs and designated with a four-letter word."

As a cancer survivor myself, and thus being quite knowledgable about drug cocktails myself. Never encountered a four-letter one: like, "FUCK", "HELL", "SHIT", "NONO." Three-lettered ones like "VIP", "BEP", will do you in...no need to add a fourth ingredient.

What a disgrace. Maybe we need to copy Parabon's geniuses on this exchange.And the NSF. Thus saving the taxpayer money.

This is the kind of crap is allowed to pass throughuniversity unscathed masquerading as a lab report.Downstream, as the crap is hired, it continues spewing nonscience.It's not their fault - management prefers hiring crap.

Thanks for the laugh here and on the 'In The Pipeline' post. I don't think we have to try to figure out what the technology is here except for laughs. If a press release can't do the simple task of getting that across to experts in the field, then the people and company behind it don't deserve things like NSF grants.

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